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Figure 1 Potential for differentiation with small molecules Detailed investigation of the small molecule GLP-1 receptor agonist danuglipron showed that, compared to natural GLP-1, the synthetic agonist showed differences in GPCR coupling to the cAMP and B-arrestin downstream biological pathways
Wei P, Yang Y, Li T, Ding Q, Sun H
However, an 18.7% efficiency decline was observed between 24 and 120 h, which was attributed to synergistic factors: (1) arrhenius-driven thermal deactivation of LCC (E a = 58.2 kJmol 1 ) and (2) TPA-induced acidification (pH 1.8) causing non-competitive inhibition, as evidenced by 3.2-fold K m increase and 68% V max reduction
Across these trials, tirzepatide delivered dose-dependent improvements in glycemic control and body weight, often surpassing comparators like semaglutide and dulaglutide (43)(44)
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